Respirable PLGA microspheres containing rifampicin for the treatment of tuberculosis: Manufacture and characterization

Purpose. Particles with aerodynamic diameters of 1-5 mu m deposit in the pe riphery of the lungs and are phagocytized by alveolar macrophages, the prim ary site of Mycobacterium tuberculosis infection. Aerosols of biodegradable polymeric microspheres containing antitubercular agents may be delivered t o the lungs to improve the treatment of tuberculosis. Methods. Poly(lactide-co-glycolide) (PLGA) microspheres containing rifampic in were prepared using solvent evaporation and spray drying methods. The so lvent evaporation process was optimized using factorial experimental design and surface response methodology. The morphology, particle size, drug load ing, and dissolution of microspheres was evaluated. Results. The spray dried rifampicin loaded PLGA microparticles were shrivel ed, unlike the spherical particles produced by solvent evaporation. Drug lo adings of 20% and 30% were achieved for solvent evaporation and spray dried products, respectively. The particles prepared by solvent evaporation and spray drying had 3.45 mu m and 2.76 mu m median diameters by volume, respec tively. Conclusions. Respirable rifampicin loaded PLGA microspheres were produced b y both solvent evaporation and spray drying methods. These particles are be ing evaluated in an animal model of tuberculosis.